人类孕烷受体遗传变异对遗传药理学和药物代谢的影响  

Effects of genetics variants of pregnant xenobiotic receptor and on pharmacogenetics and drug metabolism

作　　者：刘艳[1] 尹又[2] 陈尧[3] 周宏灏[3] 

机构地区：[1]上海交通大学附属新华医院药剂科,上海200092 [2]上海长征医院神经内科,上海200003 [3]中南大学临床药理研究所

出　　处：《中国临床药理学与治疗学》2007年第8期845-849,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(30572226)

摘　　要：CYP3A4和多药耐药相关基因(MDR1)等在药物清除和处置中起重要调节作用,孕烷受体(PXR)通过调节上述基因间接影响药物诱导反应。因此,PXR的基因变异会对临床药物-药物相互作用产生极其重要的影响。本文将对目前已经发现的PXR基因变异及突变导致的功能影响作一综述。同时,因为可变剪接在个体差异和组织特异性表达中起着不可或缺的作用,本文将一并讲述。全面考虑PXR的基因突变和mRNAs可变剪接最终将有助于评价药物联合运用合理性和推测药物治疗效应。The orphan nuclear receptor PXR influence drug-induced effects indirectly by mediating transcription of genes CYP3A4 and MDR1 which play important roles in drug clearance and disposition. Thus, genetic variability in PXR will contribute significantly to drugdrug interactions in clinical practice. This review describes common PXR genetic variants that have been identiffed to date in the human population and the functional consequence of these variant alleles. In addition, this article also described alternatively spliced variants of PXRwhich may also contribute to individual variability as well as tissue specific expression. Identification of PXR genetic variants and alternatively spliced＇mRNAs may ultimately conduce to the evaluation of rationality when drugs given in combination and the predictions of therapeutic effects.

关 键 词：孕烷受体 变异 单核苷酸多态性 可变剪接 药物代谢 遗传药理学 

分 类 号：R968[医药卫生—药理学] R969.1[医药卫生—药学]